FACTORS ASSOCIATED TO THERAPEUTIC FAILURE OF LOSARTAN IN PATIENTS WITH HEART FAILURE. PHARMACOKINETIC MODEL

Abstract

BackgroundDecompensated heart failure is a common cause of hospitalization. Therapeutic use of ARA‐II has demonstrated safety in this patients. Circulating drug concentrations can be affected by some factors (age, sex, body surface, formulation), and variations in levels of plasma can be observed, causing a therapeutic failure and therefore, greater hemodynamic instability.AimTo Identify factors that affect plasma drug concentration (Losartan patent vs generic) and its active metabolite (E‐3174) as well as possible factors that affect the therapeutic failure in patients with heart failure.MethodsA double‐blind randomized controlled clinical trial in a single dose (n = 60), comparing Losartan potassium (50 mg) patent Vs generic, This study was approved by the ethics committee, registration number 98‐15. Inclusion criteria: both sexes, stable patients with FEVI less than 40% and informed consent signed. To determine the pharmacokinetic profile, the method was validated to show compliance with international requirements ICHQ2 (R1). After oral administration of the drug, a 12‐hour follow‐up was performed. The data were analyzed by means of multiple linear regression and t‐test in RStudio.Results24/60 patients have been analyzed. Mean age 56.2 ± 13.8 years, time of evolution of HF of 1–3 years. The developed and validated analytical method proved to be sensitive, linear, accurate, precise and with fewer run‐time (5 min Vs 15 min) than the standard method. The area under the curve (AUC) of Losartan patent and generic was 3.28 ± 0.77 and 3.12 ± 0.90 (p = 0.64) respectively and for its metabolite E‐3174 patent and generic was 5.27 ± 0.89 and 4.51 ± 0.88 (p = 0.56) respectively.The maximum concentration (Cmax), was greater in the patent formulation, the metabolite E3174, was lower in male and patients with higher BMI, these data aren't a statistical difference.Conclusionsthe differences in AUC and Cmax between both formulations aren't statistically significant, however, when analyzing the metabolite E‐3174 we see that after 6 hours, the patent formulation shows an increase in the concentration that is not observed in the generic, which can affect the pharmacological effect in the patient. The therapeutic effect (blood pressure reduction) was better for patent formulation Vs generic, even without statistically significant. For these reasons is essential to complete the sample size to establish a more accurate conclusion.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.